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Streptomycin

Pronunciation

Pronunciation

(strep toe MYE sin)

Index Terms

  • Streptomycin Sulfate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intramuscular:

Generic: 1 g (1 ea)

Pharmacologic Category

  • Antibiotic, Aminoglycoside
  • Antitubercular Agent

Pharmacology

Inhibits bacterial protein synthesis by binding directly to the 30S ribosomal subunits causing faulty peptide sequence to form in the protein chain

Absorption

Oral: Poorly absorbed; IM: Well absorbed

Distribution

Distributes into most body tissues and fluids except the brain; small amounts enter the CSF only with inflamed meninges

Excretion

Urine (29% to 89% as unchanged drug); small amount (1%) excreted in bile, saliva, sweat, and tears

Time to Peak

IM: Within 1 to 2 hours

Half-Life Elimination

Newborns: 4 to 10 hours; Adults: ~2 to 4.7 hours; prolonged with renal impairment

Protein Binding

34%

Use: Labeled Indications

Tuberculosis:

Treatment of tuberculosis, in combination with other appropriate antituberculosis agents, when the primary agents (eg, isoniazid, rifampin, ethambutol, pyrazinamide) are contraindicated because of toxicity or intolerance.

Nontuberculosis infections:

Treatment of infections caused by susceptible bacteria that are not amenable to therapy with less potentially toxic agents,including sensitive Yersinia pestis (plague); Francisella tularensis (tularemia); Brucella; Klebsiella granulomatis (donovanosis, granuloma inguinale); Haemophilus ducreyi (chancroid); Haemophilus influenzae (in respiratory, endocardial, and meningeal infections, concomitantly with another antibacterial agent); Klebsiella pneumoniae pneumonia (concomitantly with another antibacterial agent); Escherichia coli, Proteus spp., Enterobacter aerogenes, K. pneumoniae, and Enterococcus faecalis in urinary tract infections; Streptococcus viridans; E. faecalis (in endocardial infections, concomitant with penicillin); and gram-negative bacillary bacteremia (concomitant with another antibacterial agent).

Use: Unlabeled

Buruli ulcer (Mycobacterium ulcerans), Ménière’s disease, Mycobacterium kansasii infection; Mycobacterium avium complex (MAC)

Contraindications

Hypersensitivity to streptomycin, other aminoglycosides, or any component of the formulation

Dosing: Adult

Note: Manufacturer’s labeling states for IM administration only, however, IV administration (off-label route) has been described (Morris 1994; Peloquin 1992; Tanoira 2014).

Usual dosage range: IM: 15 to 30 mg/kg/day or 1 to 2 g daily

Indication-specific dosing:

Brucellosis: IM: 1 g daily in 2 to 4 divided doses for 14 to 21 days (with doxycycline) (Skalsky 2008)

Endocarditis:

Enterococcal:

Manufacturer’s labeling: IM: 1 g every 12 hours for 2 weeks, followed by 500 mg every 12 hours for 4 weeks in combination with penicillin

Alternate dosing (susceptible to penicillin and streptomycin/resistant to gentamicin): Native or prosthetic valve: IM, IV: 15 mg/kg/day in divided doses every 12 hours in combination with ampicillin or penicillin; Duration of therapy: 4 weeks (native valve and symptoms present <3 months); ≥6 weeks (native valve and symptoms present ≥3 months or prosthetic valve) (AHA [Baddour 2015])

Streptococcal:Manufacturer’s labeling: IM: 1 g every 12 hours for 1 week, followed by 500 mg every 12 hours for 1 week in combination with penicillin.

Mycobacterium avium complex (MAC) (off-label use): IM: Adjunct therapy (with macrolide, rifamycin, and ethambutol): 8 to 25 mg/kg 2 to 3 times weekly for first 2 to 3 months for severe disease (maximum single dose for age >50 years: 500 mg) (Griffith 2007)

Mycobacterium avium complex (MAC) disease, disseminated in HIV-infected patients (off-label use): IM, IV: 1 g daily as optional adjunct therapy with ethambutol (plus clarithromycin or azithromycin) (HHS [OI adult 2015])

Mycobacterium kansasii disease (rifampin-resistant) (off-label use): IM: 750 mg to 1 g daily (as part of a three-drug regimen based on susceptibilities) (Campbell 2000; Griffith 2007)

Mycobacterium ulcerans (Buruli ulcers) (off-label use): IM: 15 mg/kg once daily (maximum dose: 1 g) in combination with rifampin for 8 weeks or in combination with rifampin for 4 weeks, followed by 4 weeks of rifampin and clarithromycin (WHO 2012)

Plague: IM:

Manufacturer’s labeling: 1 g twice daily for a minimum of 10 days.

Alternate dosing: 30 mg/kg/day (maximum dose: 2 g) divided every 12 hours until the patient is afebrile for at least 2 to 3 days. Note: Full course is considered 10 days (CDC 2014; WHO 2009).

Tuberculosis:

Manufacturer’s labeling: IM:

Daily therapy: 15 mg/kg/day (maximum: 1 g)

Directly observed therapy (DOT), twice weekly: 25 to 30 mg/kg (maximum: 1.5 g)

Directly observed therapy (DOT), 3 times weekly: 25 to 30 mg/kg (maximum: 1.5 g)

Alternate dosing: IM, IV: 15 mg/kg (maximum dose: 1 g) once daily for 5 to 7 days per week for 2 to 4 months, followed by 15 mg/kg (maximum dose: 1 g) 2 to 3 times weekly (ATS 2003)

Tularemia: IM:

Manufacturer’s labeling: 1 to 2 g daily in divided doses every 12 hours for 7 to 14 days until the patients is afebrile for 5 to 7 days

Alternative regimen: 2 g daily in 2 divided doses for ≥10 days (WHO 2007)

Dosing: Geriatric

Manufacturer’s labeling: IM: Dose reductions are necessary in patients >60 years.

Endocarditis, streptococcal: 500 mg every 12 hours for 2 weeks.

Alternate dosing: Tuberculosis: >59 years: IM, IV: 10 mg/kg (maximum: 750 mg) once daily for 5 to 7 days per week for 2 to 4 months, followed by 10 mg/kg (maximum: 750 mg) 2 to 3 times weekly (ATS 2003)

Dosing: Pediatric

Note: Manufacturer’s labeling states for IM administration only, however, IV administration (off-label route) has been described (Morris 1994; Peloquin 1992; Tanoira 2014).

Usual dosage range: Infants, Children, and Adolescents: IM: 20 to 40 mg/kg/day in divided doses every 6 to 12 hours (maximum: 1,000 mg/dose; maximum daily dose: 2,000 mg)

Indication-specific dosing: Infants, Children, and Adolescents:

Mycobacterium avium complex (MAC) disease, disseminated in HIV-infected patients (off-label use): Adolescents: Refer to adult dosing.

Mycobacterium ulcerans (Buruli ulcers) (off-label use): IM: 15 mg/kg once daily (maximum daily dose: 1,000 mg) in combination with rifampin for 8 weeks or in combination with rifampin for 4 weeks, followed by 4 weeks of rifampin and clarithromycin (WHO 2012)

Plague (off-label use): IM: 30 mg/kg/day divided every 12 hours (maximum daily dose: 2,000 mg) for 10 days or until 2 to 3 days after the temperature returns to normal (Red Book [AAP 2015]; WHO 2009)

Tularemia (off-label use): IM: 15 mg/kg twice daily (maximum daily dose: 2,000 mg) for 10 days (WHO 2007)

Tuberculosis:

Manufacturer’s labeling: IM:

Daily therapy: 20 to 40 mg/kg/day (maximum: 1,000 mg daily)

Directly observed therapy (DOT), twice weekly: 25 to 30 mg/kg (maximum: 1,500 mg)

Directly observed therapy (DOT), 3 times weekly: 25 to 30 mg/kg (maximum: 1,500 mg)

Alternate dosing: IM, IV:

Infants, Children ≤40 kg, and Adolescents <15 years or ≤40 kg:

Daily therapy: 20 to 40 mg/kg/day once daily (maximum daily dose: 1,000 mg) (ATS 2003; WHO 2009). Note: Some clinicians suggest every 12 hour dosing may be utilized (Berenberg 1951; Bradley 2015)

Directly observed therapy (DOT), twice weekly: 20 mg/kg/dose twice weekly (maximum daily dose: 1,000 mg/dose) (ATS 2003)

Children and Adolescents >40 kg or ≥15 years: 15 mg/kg/day once daily (maximum daily dose: 1,000 mg) for 5 to 7 days per week for 2 to 4 months, followed by 15 mg/kg/day (maximum daily dose: 1,000 mg) 2 to 3 times weekly (ATS 2003)

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling; however, the following adjustments have been recommended:

Adults:

Aronoff 2007: Note: Recommendations are based on doses of 1 to 2 g every 6 to 12 hours (1 g once daily for tuberculosis):

CrCl >50 mL/minute: No dosage adjustment necessary.

CrCl 10 to 50 mL/minute: Administer every 24 to 72 hours.

CrCl <10 mL/minute: Administer every 72 to 96 hours.

End-stage renal disease (ESRD):

Intermittent hemodialysis (IHD): One-half the recommended dose administered after hemodialysis on dialysis days. Note: Dosing dependent on the assumption of 3 times weekly complete IHD sessions.

Peritoneal dialysis (PD): Administration via PD fluid: 20 to 40 mg/L (20 to 40 mcg/mL) of PD fluid

Continuous renal replacement therapy (CRRT): Administer every 24 to72 hours; monitor levels. Note: Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate).

ATS 2003:

Tuberculosis:

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl <30 mL/minute: 12 to 15 mg/kg/dose (maximum dose: 1 g) 2 to 3 times weekly

End-stage renal disease (ESRD) on intermittent hemodialysis (IHD): 12 to 15 mg/kg/dose (maximum dose: 1 g) 2 to 3 times weekly.

Infants, Children, and Adolescents: Note: Recommendations are based on doses of 20 to 40 mg/kg/dose every 24 hours (Aronoff 2007)

GFR >50 mL/minute/1.73 m2: No dosage adjustment necessary.

GFR 30 to 50 mL/minute/1.73 m2: 7.5 mg/kg/dose every 24 hours.

GFR 10 to 29 mL/minute/1.73 m2: 7.5 mg/kg/dose every 48 hours.

GFR <10 mL/minute/1.73 m2: 7.5 mg/kg/dose every 72 to 96 hours.

End-stage renal disease (ESRD):

Intermittent hemodialysis (IHD): 7.5 mg/kg/dose every 72 to 96 hours

Peritoneal dialysis (PD): Administer 7.5 mg/kg/dose every 72 to 96 hours

Continuous renal replacement therapy (CRRT): Administer 7.5 mg/kg/dose every 24 hours; monitor levels. Note: Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate).

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Reconstitution

IM: Reconstitute vial with 4.2 mL,3.2 mL, or 1.8 mL sterile water for injection (SWFI) to yield a final concentration of ~ 200 mg/mL, ~250 mg/mL, or ~400 mg/mL, respectively

IV: Further dilute dose to concentration of 5 to 10 mg/mL in D5W or NS (Morris 1994; Peloquin 1992; Tanoira 2014)

Administration

IM: Inject deep IM into large muscle mass; midlateral thigh muscle (preferred site for children); midlateral thigh muscle or upper outer quadrant of buttocks (adults); rotate injection sites.

IV (off-label route): After dilution in admixture, infuse over 30 to 60 minutes (Morris 1994; Peloquin 1992; Tanoira 2014)

Compatibility

Compatibility in syringe: Incompatible: Heparin

Storage

Store intact vials at 20°C to 25°C (68°F to 77°F). Protect from light. Reconstituted solution may be stored at room temperature for up to 1 week.

Depending upon manufacturer, reconstituted solution remains stable for 24 hours at room temperature. Exposure to light causes darkening of solution without apparent loss of potency.

Drug Interactions

AbobotulinumtoxinA: Aminoglycosides may enhance the neuromuscular-blocking effect of AbobotulinumtoxinA. Monitor therapy

Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Arbekacin: May enhance the nephrotoxic effect of Aminoglycosides. Arbekacin may enhance the ototoxic effect of Aminoglycosides. Monitor therapy

Bacitracin (Systemic): Streptomycin may enhance the nephrotoxic effect of Bacitracin (Systemic). Avoid combination

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Bisphosphonate Derivatives: Aminoglycosides may enhance the hypocalcemic effect of Bisphosphonate Derivatives. Monitor therapy

Capreomycin: May enhance the neuromuscular-blocking effect of Aminoglycosides. Monitor therapy

CARBOplatin: Aminoglycosides may enhance the ototoxic effect of CARBOplatin. Especially with higher doses of carboplatin. Monitor therapy

Cefazedone: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Cephalosporins (2nd Generation): May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Cephalosporins (3rd Generation): May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Cephalosporins (4th Generation): May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Cephalothin: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Cephradine: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Avoid combination

CISplatin: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Colistimethate: Aminoglycosides may enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate. Consider therapy modification

CycloSPORINE (Systemic): Aminoglycosides may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Monitor therapy

Distigmine: Aminoglycosides may diminish the therapeutic effect of Distigmine. Monitor therapy

Foscarnet: May enhance the nephrotoxic effect of Aminoglycosides. Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Loop Diuretics: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Monitor therapy

Mannitol (Systemic): May enhance the nephrotoxic effect of Aminoglycosides. Avoid combination

Mecamylamine: Aminoglycosides may enhance the neuromuscular-blocking effect of Mecamylamine. Avoid combination

Neuromuscular-Blocking Agents: Aminoglycosides may enhance the respiratory depressant effect of Neuromuscular-Blocking Agents. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May decrease the excretion of Aminoglycosides. Data only in premature infants. Monitor therapy

OnabotulinumtoxinA: Aminoglycosides may enhance the neuromuscular-blocking effect of OnabotulinumtoxinA. Monitor therapy

Oxatomide: May enhance the ototoxic effect of Aminoglycosides. Monitor therapy

Penicillins: May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Exceptions: Amoxicillin; Ampicillin; Cloxacillin; Dicloxacillin; Nafcillin; Oxacillin; Penicillin G (Parenteral/Aqueous); Penicillin G Benzathine; Penicillin G Procaine; Penicillin V Potassium. Consider therapy modification

RimabotulinumtoxinB: Aminoglycosides may enhance the neuromuscular-blocking effect of RimabotulinumtoxinB. Monitor therapy

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

Tenofovir Products: Aminoglycosides may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Aminoglycosides. Monitor therapy

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Adverse Reactions

Frequency not defined.

Cardiovascular: Hypotension

Central nervous system: Drug fever, facial paresthesia, headache, neurotoxicity

Dermatologic: Exfoliative dermatitis, skin rash, urticaria

Gastrointestinal: Nausea, vomiting

Genitourinary: Azotemia, nephrotoxicity

Hematologic & oncologic: Eosinophilia, hemolytic anemia, leukopenia, pancytopenia, thrombocytopenia

Hypersensitivity: Anaphylaxis, angioedema

Neuromuscular & skeletal: Arthralgia, tremor, weakness

Ophthalmic: Amblyopia

Otic: Auditory ototoxicity, vestibular ototoxicity

Respiratory: Dyspnea

<1% (Limited to important or life-threatening): DRESS syndrome (drug reaction with eosinophilia and systemic symptoms), toxic epidermal necrolysis

ALERT: U.S. Boxed Warning

Toxicity:

The risk of severe neurotoxic reactions is sharply increased in patients with impaired renal function or prerenal azotemia. These include disturbances of vestibular and cochlear function, optic nerve dysfunction, peripheral neuritis, arachnoiditis, and encephalopathy. The incidence of clinically detectable, irreversible vestibular damage is particularly high in patients treated with streptomycin.

Renal function should be monitored carefully; patients with renal impairment and/or nitrogen retention should receive reduced doses. The peak serum concentration in individuals with kidney damage should not exceed 20 to 25 mcg/mL.

The concurrent or sequential use of other neurotoxic and/or nephrotoxic drugs with streptomycin, including neomycin, kanamycin, gentamicin, cephaloridine, paromomycin, viomycin, polymyxin B, colistin, tobramycin, and cyclosporine should be avoided.

The neurotoxicity of streptomycin can result in respiratory paralysis from neuromuscular blockage, especially when the drug is given soon after the use of anesthesia or muscle relaxants.

The administration of streptomycin in parenteral form should be reserved for patients where adequate laboratory and audiometric testing facilities are available during therapy.

Warnings/Precautions

Concerns related to adverse effects:

• Neuromuscular blockade and respiratory paralysis: [US Boxed Warning]: May cause neuromuscular blockade and respiratory paralysis; especially when given soon after anesthesia or muscle relaxants.

• Neurotoxicity: [US Boxed Warning]: May cause neurotoxicity, including disturbances of vestibular and cochlear function, optic nerve dysfunction, peripheral neuritis, arachnoiditis, and encephalopathy; usual risk factors include pre-existing renal impairment, concomitant neuro-/nephrotoxic medications. Ototoxicity is proportional to the amount of drug given and the duration of treatment. Tinnitus or vertigo may be indications of vestibular injury and impending bilateral irreversible damage. Baseline and periodic caloric stimulation and audiometric tests are recommended with prolonged therapy. Discontinue treatment if signs of ototoxicity occur.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Hearing impairment: Use with caution in patients with pre-existing vertigo, tinnitus, or hearing loss.

• Neuromuscular disorders: Use with caution in patients with neuromuscular disorders, including myasthenia gravis.

• Renal impairment: [US Boxed Warning]: May cause nephrotoxicity. Use with caution in patients with renal impairment; dose adjustment necessary in patients with renal impairment and/or nitrogen retention. Monitor renal function closely; peak serum concentrations should not surpass 20 to 25 mcg/mL in patients with renal impairment.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information

• Neurotoxic and/or nephrotoxic drugs: [US Boxed Warning]: Avoid concomitant or sequential use with other neurotoxic and/or nephrotoxic drugs (eg, neomycin, kanamycin, gentamicin, paromomycin, polymyxin B, colistin, tobramycin, cyclosporine).

Dosage form specific issues:

• Sulfite sensitivity: Some formulations may contain sodium metabisulfite; may cause allergic reactions including anaphylaxis or asthma exacerbations (some life-threatening) in susceptible patients.

Other warnings/precautions:

• Appropriate use: [US Boxed Warning]: Parenteral form should be used only where appropriate audiometric and laboratory testing facilities are available. IM injections should be administered in a large muscle well within the body to avoid peripheral nerve damage and local skin reactions.

Monitoring Parameters

Baseline and periodic hearing tests (audiograms), BUN, creatinine; serum drug concentrations should be monitored in all patients

Pregnancy Risk Factor

D

Pregnancy Considerations

Streptomycin crosses the placenta. Streptomycin may cause fetal harm if administered to a pregnant woman. There are multiple reports of total irreversible bilateral congenital deafness in children whose mothers received streptomycin during pregnancy. Streptomycin should never be substituted as first line therapy for the treatment of tuberculosis in pregnant women (Blumberg 2003).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience diarrhea. Have patient report immediately to prescriber signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, or weight gain), change in balance, confusion, nausea, vomiting, dizziness, passing out, headache, hearing loss, twitching, seizures, difficulty breathing, slow breathing, shallow breathing, vision changes, loss of strength and energy, burning or numbness feeling, tinnitus, or signs of Clostridium difficile (C. diff)-associated diarrhea (stomach pain or cramps, very loose or watery stools, or bloody stools) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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